Double-blind, randomized, placebo-controlled Canadian multicenter trial of two doses of synthetic surfactant or air placebo in 224 infants weighing 500 to 749 grams with respiratory distress syndrome. Canadian Exosurf Neonatal Study Group.

In a multicenter, double-masked, placebo-controlled rescue trial conducted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 224 infants with birth weights of 500 to 749 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio of less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical ventilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and in mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placebo group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo group vs synthetic surfactant group; p = 0.089) nor the incidence of survival without BPD through 28 days (17% vs 26%, respectively; p = 0.070) was significantly different in the two groups. No significant differences in the incidence of safety-related outcomes or in adverse effects such as apnea or pulmonary hemorrhage were noted. These findings indicate that rescue therapy with synthetic surfactant results in physiologic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress syndrome were not documented in the sample evaluated.

Reliability of interpretation of cranial ultrasound examinations of very low-birthweight neonates.

The authors studied intra- and inter-reader reliability of the interpretation of cranial ultrasound examinations of very low-birthweight infants. A radiologist read 173 films, 88 of which he had read previously; the other 85 had been read previously by a second radiologist. For the diagnoses of subependymal hemorrhage and intraventricular hemorrhage, intra-reader agreement was similar to inter-reader agreement. 98 ultrasound films were read initially as showing subependymal hemorrhage; in nine cases the second reading did not agree. In five of 58 cases read initially as showing intraventricular hemorrhage, the second reading did not agree. Similarly, of 32 cases read initially as showing intraparenchymal echo-density, four were interpreted as negative on second reading. For all three diagnoses, disagreement occurred often enough to cause substantial misclassification bias when cranial ultrasound is used for clinical research.

Effects of two rescue doses of a synthetic surfactant on mortality rate and survival without bronchopulmonary dysplasia in 700- to 1350-gram infants with respiratory distress syndrome. The American Exosurf Neonatal Study Group I.

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 21 American hospitals, two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air were administered to 419 infants weighing 700 to 1350 gm who had respiratory distress syndrome and an arterial/alveolar oxygen pressure ratio less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to those infants remaining on ventilatory support. Infants were stratified at entry by birth weight and gender. Among infants receiving synthetic surfactant, improvements in alveolar-arterial oxygen pressure gradient, arterial/alveolar oxygen pressure ratio, and oxygen and ventilator needs through 7 days of age were apparent. Death from respiratory distress syndrome was reduced by two thirds (21 vs 7; p = 0.007), and the overall neonatal mortality rate was reduced by half (50 vs 23; p = 0.001). Although there was no significant reduction in the incidence of bronchopulmonary dysplasia (39 vs 31; p = 0.107), the hypothesis that survival through 28 days without bronchopulmonary dysplasia would be enhanced by two rescue doses of synthetic surfactant was proved true (21% improvement, from 132 to 156 patients; p = 0.001). In addition, the incidence of pneumothorax was reduced by one third (62 vs 40; p = 0.022), and the incidence of pulmonary interstitial emphysema was reduced by half (102 vs 51; p = 0.001). The only side effect identified was an increase in the incidence of apnea (102 vs 134; p = 0.001). These findings indicate that rescue use of a synthetic surfactant can improve the morbidity and mortality rates for premature infants with respiratory distress syndrome.

Ultrasonography of discoid adrenals in Potter's syndrome: report of three cases.

Potter's syndrome, a rapidly fatal congenital disorder marked by renal agenesis, can be diagnosed in the first hours of life with real-time ultrasound. In infants with Potter's syndrome the adrenal glands assume a discoid shape and occupy the renal beds, thereby mimicking the absent kidneys. However, discoid adrenals can be distinguished from either normal or dysplastic kidneys by definitive ultrasound criteria. The ultrasound appearance of an echogenic medulla and a hypoechoic cortex in a posteriorly placed, flattened adrenal gland is quite different from the neonatal kidney with its echogenic cortex and hypoechoic renal pyramids. Early diagnosis is desirable to facilitate management of this hopeless condition. Difficulties with reliable antenatal ultrasonographic diagnosis of Potter's syndrome are discussed.

The significance of ventriculomegaly in the newborn with myelodysplasia.

Hydrocephalus occurs in 69% to 92% of the meningomyelocele population, but rarely becomes manifest until after the meningomyelocele is closed. Ventriculomegaly is common at birth, even in neonates without overt hydrocephalus. Thus, palpating the anterior fontanel and cranial sutures and measuring the head circumference may be misleading. We report a means of identifying spina bifida neonates who will subsequently develop hydrocephalus. Dubowitz gestational age, birth weight, birth head circumference, head circumference percentile, and the lateral ventricular ratio (LVR) from ultrasonograms were analyzed for each of 25 neonates with meningomyelocele. The mean head circumference percentile was 47.7 +/- 7.7 SE (range: less than 5 to greater than 95). Ventriculomegaly, however, defined by an LVR of greater than 0.32, was present in all but 2 of the neonates. Pearson's correlation test showed that only one-third of the elevated LVRs could be explained by the head circumference. Later ventricular shunting was eventually required in all but 3 infants. We concluded that (1) clinical examination of the myelodysplastic neonate usually does not reveal evidence of hydrocephalus and (2) ventriculomegaly on ultrasonography predicts the later development of hydrocephalus following meningomyelocele closure.

Chronic lung disease in children referred to a teaching hospital.

Etiology, symptomatology, and host factors were studied in 184 children referred to a teaching hospital for evaluation in an attempt to classify chronic or potentially chronic lung disease. A standardized historical questionnaire, physical findings, chest radiographs, and a laboratory panel identified a diagnosis that could be related directly or indirectly to chronic lung disease in 22% of the subjects. Among the remaining 78%, bronchiectasis was found in 9%, chronic pneumonia in 9%, chronic diseases with wheezing in 56%, and no significant lower respiratory disease in 4%. Analysis of cases with no apparent etiology revealed that the majority of patients had historical evidence of wheezing; often this previously had not been appreciated. Laboratory tests, such as eosinophil count and immunoglobulin E (IgE) testing, did not differentiate between wheezing and nonwheezing patients. Spirometric evaluation was limited because most subjects were younger than 5 years old. For the same reason, testing for bronchial hyperreactivity was not done. This study reemphasizes that wheezing is a major symptom of chronic lung disease in childhood and provides an outline for its evaluation. Although clinical airways reactivity, as exemplified by wheezing, proved to be the most prominent host defect found in this study, its nature, genetic or otherwise, remains to be defined.

Childhood Menetrier's disease: four new cases and discussion of the literature.

Four cases of childhood Menetrier's disease are presented and their clinical and laboratory findings are compared with the other childhood cases reported in the literature. Children with Menetrier's disease usually present with abdominal pain or nausea and vomiting associated with peripheral edema, ascites, or pleural effusion; these symptoms are due to gastrointestinal protein loss and resultant hypoproteinemia. There is no evidence of urinary protein loss. The favorable clinical course as well as distinctive laboratory and roentgenologic findings distinguish this entity from other causes of these symptoms. Supportive therapy is normally all that is required since the symptoms resolve spontaneously in weeks to months. Surgery may be needed in rare cases of active gastrointestinal hemorrhage.

Unilateral duplex horseshoe kidney with ectopic ureterocele.

We have reported a case of horseshoe kidney, a common renal fusion anomaly. Because of the 25% incidence of associated genitourinary anomalies, we believe that the diagnosis of horseshoe kidney in pediatric patients should initiate a thorough urologic evaluation, including intravenous urography and real-time sonography.

Hypophosphatasia and nephrocalcinosis demonstrated by ultrasound and CT.

A case of medullary type of nephrocalcinosis in hypophosphatasia is presented. Sonography revealed medullary calcification not visible on abdominal radiography. Calcification could also be demonstrated by CT scanning.

Unreliability of radiographic diagnosis of septic hip in children.

The radiographs of 19 pediatric patients with aspiration-proven bacterial infections of the hip were analyzed. The hip radiograph was abnormal in all neonates showing lateral subluxation. The radiograph was negative in eight of ten children more than 1 year of age. It is emphasized that children with suspected septic hip require immediate joint aspiration regardless of radiographic findings.

A computer-assisted radiologic reporting system.

The patient registration and interpretation/reporting modules of a computer-assisted radiologic reporting system are described. Entries may be made at several levels of complexity, using bar codes or keyboard input. Several functions allow convenient access to the database. Output may be reformatted without programmer intervention via a maintenance file. The system allowed improved turnaround time, reduced costs, and better understanding of work patterns.

Malignant histiocytosis presenting as interstitial pulmonary disease.

Three children presented with progressive respiratory symptoms and radiographic evidence of diffuse interstitial infiltrates. All three had a pulmonary pathologic diagnosis of malignant histiocytosis. The pulmonary manifestations of this disease appear to have been responsive to combined chemotherapy. Malignant histiocytosis needs to be considered in the differential diagnosis of interstitial pulmonary disease.